SSRIs in Perspective

Have They Lived up to Their Promise?

John Preston

The research literature on the effectiveness of antidepressants is filled with contradictions and controversy. Few have the scientific know-how and patience to wade into the Great SSRI Debate and make sense of it. An exception is neuropsychologist John Preston, author of Clinical Psychopharmacology Made Ridiculously Easy. While he’s a critic of the role of Big Pharma in the mental health field, in the interview below, he tells us how SSRIs may have unfairly gotten a bad rep.

Depression is probably the number-one condition for which people receive psychiatric medication. What’s the overall incidence of depression in the general population and, from a psychopharmacology viewpoint, what are the main distinctions among different kinds of depression?

John Preston: At any moment in the United States, 10 percent of people are in the midst of some kind of severe mood disorder. The lifetime prevalence for unipolar major depression is judged to be about 15 percent, and then about 5 percent of some people have some version of bipolar disorder. So we’re looking at somewhere between 15 and 20 percent of people.

Bipolar disorder, of course, presents with both depressions and either manias or hypomanias. But this isn’t just an academic question about the right diagnosis. It’s been clearly shown that if people who have bipolar disorder are treated with some of the standard antidepressant medications, the outcomes are not good. Unfortunately, a great number of these people are misdiagnosed as having more garden-variety unipolar depressions and given antidepressants, which not only don’t work, but can make a bipolar disorder worse, either increasing the frequency of episodes or causing mania. The current estimate is that the lifetime prevalence for bipolar II is about 4 percent, which is four times the incidence of the traditional manic-depressive bipolar I disorder we learned about in grad school.

Antidepressants have gotten terrible press in recent years. Studies show that they’re not much more effective than placebos, and many studies with negative outcomes were financed by the drug companies and never saw the light of day. As therapists, what conclusions should we draw from these findings?

Preston: From the get-go we should acknowledge the obvious: drug companies want to make money, and it’s been estimated that 75 percent of the outcome studies on antidepressants have been funded by drug companies. So that’s a good reason to be skeptical about this research. The most comprehensive meta-analytic that first came out in 2002 found that the outcome with antidepressants was only slightly better than with placebos. The results were statistically significant enough to meet the standards for approval required by the FDA, but just barely. In those studies, somewhere between 25 to 30 percent of people who take antidepressants have a positive placebo response, whereas somewhere between 30 to 40 percent of people who take antidepressants have a positive response. So while the separation between placebo and drug is tiny, it’s good enough for the FDA. But there’s more to the story.

To meet the FDA requirements in that research, all that was needed to get a drug licensed was two or three studies with large enough sample sizes showing superiority over placebo. At weeks 1 and 2, as you might expect, the placebo and drug typically looked very similar, but by weeks 3 or 4, the drug usually looked a little bit better. And by the time there was enough difference between the placebo and the drug to be statistically significantly different, they stopped the study. In more than 90 percent of the studies, the data were based on only four- to six-week trials, at which point the studies were stopped because they cost a lot of money to keep running, and—from the viewpoint of the drug companies—they’d achieved their aim of showing the drug was just little bit better than placebo and therefore could be approved.